Epstein-Barr- Skildum

Question 1

What are the classic triad of symptoms for mononucleosis?

Answer 1

Pharyngitis
Lymphadenopathy
Fever

Question 2

What is a definitive test for mononucleosis? How does it work?

Answer 2

Monospot test- looks for agglutination of horse/sheeps blood

Since EBV latent infection is in B-cells, produce many hereophile Ab which cause agglutination

Question 3

What are heterophile antibodies?

Answer 3

Many abs of differing antigen specificty, produced by the polyclonal expansion of B cells

Question 4

How would you distinguish an acute from a previous EBV infection?

Answer 4

Acute infection = IgM in blood to VCA (viral capsid antigen)

Previous infection = IgG in blood to VCA

Question 5

Describe EBV

Answer 5

dsDNA, circular genome tethered to host chromosome

enveloped

Icosahedral capsid symmetry

Tropism for eptithelial cells of oropharynx, latent in B-cells

Question 6

Describe the lifecycle of EBV, be specific!

Answer 6

Viral envelope proteins gp350/220 bind to C3d complement receptor to initiate endocytosis

Genome circularizes, expresses different genes for acute and latenet infection

Viral particle buds through cellular membranes

Question 7

Function of EBV viral oncogene LMP-1?

Answer 7

Encoded during latent infection, expressed on surface of B-cells

Functions as an “always on” CD40 – causes antigen independent activation of B-cells

(CD40 normally responsible for CD4+ Tcell dependent activation of B cells)

PROMOTES TRANSCRIPTION OF NFkB genes

Question 8

Function of EBV viral oncogene LMP-2?

Answer 8

functions as “always on” B-cell receptor

(normally responsible for ANTIGEN dependent B-cell activation)

Promotes MAPK activation, and activates fox/jun transcription factors

Question 9

Function of EBV viral oncogene EBNA3C?

Answer 9

Binds and activates cyclin D1 complexes, results in

hyperphosphorylation of Rb protein
Activation of E2F family TF
Expression of genes that control DNA replication
Cell cycle progression

Question 10

Molecular pathophysiology of X-linked lymphoproliferative diesease

Answer 10

Mutation = non-functional SAP protein

SAP normally recruits kinases to immunological synapse (normally turns signal off after infection)

Loss of SAP = deficiency of IL-4 production by T-cells

SAP controls apoptic death of activated T-cells = mechanism for stopping the immune response once pathogen is gone

Basically immune system has NO BREAKS